The overall goals of the project are to understand the kinetics and control of production of neutrophilic leukocytes and of hematopoietic stem cells. Human studies are primarily designed to understand the kinetic changes that lead to neutropenia and especially to characterize and distinguish the various forms of congenital neutropenia. In mice we are studying a variety of systems. Hepatic hematopoiesis is induced in adult mice by treating them with methylcellulose and the kinetics of this form of extramedullary hematopoiesis are characterized. Other methods of inducing this, such as inducing myelosclerosis with estrone, are under study. Further studies of the nature of the defects leading to hypoplastic anemia in W/Wv and SL/SLd mice will be done. An effective hematopoietic microenvironment is formed when cellulose acetate discs are coated by peritoneal cells. When animals bearing such discs are irradiated and injected i.p. with marrow cells, colonies of granulocytes and erythrocytes grow on the disc. We are attempting to characterize factors which influence colony growth. The C3H/HeJ mouse is very resistant to many effects of endotoxin unlike its parent strain of C3H. Using these mice in crossing experiments and by cross marrow transplants we hope to characterize the genetic control and interrelation of control points in the stem cell -neutrophil system.